The present invention generally relates to processes for preparing paclitaxel. More specifically, the present invention relates to processes for the preparation of paclitaxel including the protection of the C(7) and the C(10) hydroxy groups of 10-deacetylbaccatin III (10-DAB) using a bridging silicon-based protecting group.
10-DAB (1), which is extracted from the needles of the English yew (taxus baccata L.) is a key starting material in the production of taxol (also known as paclitaxel) and docetaxel (Taxotere®), both of which are potent anticancer agents.

Conversion of 10-DAB to a cytotoxically active taxane requires selective derivatization of the C(13) hydroxy group to form a C(13) ester side chain. Because 10-DAB is a polyol and because each of these hydroxy groups is not equally reactive under a defined set of conditions, preparation of taxol or docetaxel from 10-DAB typically requires selective protection and/or derivatization of the C(7) and the C(10) hydroxy groups before the C(13) side chain is attached.
Early strategies for the preparation of taxol, docetaxel and other taxanes from 10-DAB were based on the observation of Senilh et al. (C.R. Acad. Sci. Paris, IT, 1981, 293, 501) that the relative reactivity of the four hydroxy groups of 10-DAB toward acetic anhydride in pyridine is C(7)-OH>C(10)-OH>C(13)-OH>C(1)-OH. Denis et al. reported (J. Am. Chem. Soc., 1988, 110, 5917) selective silylation of the C(7) hydroxy group of 10-DAB with triethylsilyl chloride in pyridine to give 7-triethylsilyl-10-deacetyl baccatin (III) in 85% yield.
More recently, Holton et al. disclosed in U.S. Pat. No. 6,191,287 that the relative reactivity toward acetic anhydride as between C(7) and C(10) is different in the presence of a Lewis acid than it is in the presence of base. Holton et al. described processes for the selective derivatization of the C(7) or the C(10) hydroxy group of 10-DAB and other taxanes, wherein the C(10) hydroxy group may be protected or derivatized prior to the C(7) hydroxy group. Specifically, Holton et al. described a process for acylating or silylating the C(10) hydroxy group prior to acylating, silylating, or ketalizing the C(7) hydroxy group.